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Theophylline is a brand name for Theophylline. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: INDICATIONS AND USAGE: Theophylline extended-release tablets are indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.
Verbatim from this product's FDA label. Tap a section to expand.
DOSAGE AND ADMINISTRATION:
Taking theophylline extended-release tablets immediately after a high-fat content meal may result in a somewhat higher C max and delayed T max and somewhat greater extent of absorption. However, the differences are usually not great and this product may normally be administered without regard to meals (see CLINICAL PHARMACOLOGY, Drug interactions, Drug-Food Interactions ).
Theophylline extended-release tablets are recommended for chronic or long-term management and prevention of symptoms, and not for use in treating acute symptoms of asthma and reversible bronchospasm.
General considerations:
The steady-state peak serum theophylline concentration is a function of the dose, the dosing interval, and the rate of theophylline absorption and clearance in the individual patient. , 400- 1600 mg/day in adults <60 years old and 10-36 mg/kg/day in children 1-9 years old).
For a given population there is no single theophylline dose that will provide both safe and effective serum concentrations for all patients. Administration of the median theophylline dose required to achieve a therapeutic serum theophylline concentration in a given population may result in either sub-therapeutic or potentially toxic serum theophylline concentrations in individual patients.
For example, at a dose of 900 mg/d in adults <60 years or 22 mg/kg/d in children 1-9 years, the steady-state peak serum theophylline concentration will be <10 mcg/mL in about 30% of patients, 10-20 mcg/mL in about 50% and 20-30 mcg/mL in about 20% of patients.
The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects. Transient caffeine-like adverse effects and excessive serum concentrations in slow metabolizers can be avoided in most patients by starting with a sufficiently low dose and slowly increasing the dose, if judged to be clinically indicated , in small increments (see Table V).
Dose increases should only be made if the previous dosage is well tolerated and at intervals of no less than 3 days to allow serum theophylline concentrations to reach the new steady state. Dosage adjustment should be guided by serum theophylline concentration measurement (see PRECAUTIONS, Laboratory Tests and DOSAGE AND ADMINISTRATION, Table VI ).
ADVERSE REACTIONS:
Adverse reactions associated with theophylline are generally mild when peak serum theophylline concentrations are <20 mcg/mL and mainly consist of transient caffeine-like adverse effects such as nausea, vomiting, headache, and insomnia.
When peak serum theophylline concentrations exceed 20 mcg/mL, however, theophylline produces a wide range of adverse reactions including persistent vomiting, cardiac arrhythmias, and intractable seizures which can be lethal (see OVERDOSAGE ).
,>300 mg/day in adults and >12 mg/kg/day in children beyond 1 year of age). During the initiation of theophylline therapy, caffeine-like adverse effects may transiently alter patient behavior, especially in school age children, but this response rarely persists.
Initiation of theophylline therapy at a low dose with subsequent slow titration to a predetermined age-related maximum dose will significantly reduce the frequency of these transient adverse effects (see DOSAGE AND ADMINISTRATION, Table V ).
, 10-20 mcg/mL). Other adverse reactions that have been reported at serum theophylline concentrations <20 mcg/mL include diarrhea, irritability, restlessness, fine skeletal muscle tremors, and transient diuresis. In patients with hypoxia secondary to COPD, multifocal atrial tachycardia and flutter have been reported at serum theophylline concentrations 15 mcg/mL.
There have been a few isolated reports of seizures at serum theophylline concentrations <20 mcg/mL in patients with an underlying neurological disease or in elderly patients. The occurrence of seizures in elderly patients with serum theophylline concentrations <20 mcg/mL may be secondary to decreased protein binding resulting in a larger proportion of the total serum theophylline concentration in the pharmacologically active unbound form.
WARNINGS:
Concurrent Illness: Theophylline should be used with extreme caution in patients with the following clinical conditions due to the increased risk of exacerbation of the concurrent condition: Active peptic ulcer disease Seizure disorders Cardiac arrhythmias (not including bradyarrhythmias) Conditions that Reduce Theophylline Clearance: There are several readily identifiable causes of reduced theophylline clearance.
If the total daily dose is not appropriately reduced in the presence of these risk factors, severe and potentially fatal theophylline toxicity can occur. Careful consideration must be given to the benefits and risks of theophylline use and the need for more intensive monitoring of serum theophylline concentrations in patients with the following risk factors: Age: Neonates (term and premature), Children <1 year, Elderly (>60 years) Concurrent Diseases: Acute pulmonary edema, congestive heart failure, cor-pulmonale, fever (≥102° for 24 hours or more; or lesser temperature elevations for longer periods), reduced renal function in infants <3 months of age, sepsis with multi-organ failure and shock.
, carbamazepine, rifampin). (see PRECAUTIONS, Drug Interactions, Table II ).
When Signs or Symptoms of Theophylline Toxicity Are Present:
Whenever a patient receiving theophylline develops nausea or vomiting, particularly repetitive vomiting, or other signs or symptoms consistent with theophylline toxicity (even if another cause may be suspected), additional doses of theophylline should be withheld and a serum theophylline concentration measured immediately.
Patients should be instructed not to continue any dosage that causes adverse effects and to withhold subsequent doses until the symptoms have resolved, at which time the healthcare professional may instruct the patient to resume the drug at a lower dosage (see DOSAGE AND ADMINISTRATION, Dosing Guidelines, Table VI).
CONTRAINDICATIONS:
Theophylline extended-release tablets are contraindicated in patients with a history of hypersensitivity to theophylline or other components in the product.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Health care providers should instruct patients and care givers to discontinue any dosage that causes adverse effects, to withhold the medication until these symptoms are gone and to then resume therapy at a lower, previously tolerated dosage (see WARNINGS ).
If the patient's symptoms are well controlled, there are no apparent adverse effects, and no intervening factors that might alter dosage requirements (see WARNINGS and PRECAUTIONS ), serum theophylline concentrations should be monitored at 6 month intervals for rapidly growing children and at yearly intervals for all others.
, every 24 hours. Theophylline distributes poorly into body fat, therefore, mg/kg dose should be calculated on the basis of ideal body weight. Table V contains theophylline dosing titration schema recommended for patients in various age groups and clinical circumstances.
Table VI contains recommendations for theophylline dosage adjustment based upon serum theophylline concentrations. Application of these general dosing recommendations to individual patients must take into account the unique clinical characteristics of each patient.
In general, these recommendations should serve as the upper limit for dosage adjustments in order to decrease the risk of potentially serious adverse events associated with unexpected large increases in serum theophylline concentration.
A. Children (6-15 years) and adults (16-60 years) without risk factors for impaired clearance Table V. Dosing initiation and titration (as anhydrous theophylline)* Titration Step Children < 45 kg Children > 45 kg and adults 1 Starting Dosage 12-14 mg/kg/day up to a maximum of 300 mg/day divided Q12 hrs* 300 mg/day divided Q12 hrs* 2 After 3 days, if tolerated , increase dose to: 16 mg/kg/day up to a maximum of 400 mg/day divided Q12 hrs* 400 mg/day divided Q12 hrs* 3 After 3 more days, if tolerated , increase dose to: 20 mg/kg/day up to a maximum of 600 mg/day divided Q12 hrs* 600 mg/day divided Q12 hrs* B.
Patients With Risk Factors For Impaired Clearance, The Elderly (>60 Years), And Those In Whom It Is Not Feasible To Monitor Serum Theophylline Concentrations: In children 6-15 years of age, the final theophylline dose should not exceed 16 mg/kg/day up to a maximum of 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS ) or if it is not feasible to monitor serum theophylline concentrations.
In adolescents ≥16 years and adults, including the elderly, the final theophylline dose should not exceed 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS ) or if it is not feasible to monitor serum theophylline concentrations.
* Patients with more rapid metabolism, clinically identified by higher than average dose requirements, should receive a smaller dose more frequently (every 8 hours) to prevent breakthrough symptoms resulting from low trough concentrations before the next dose.
Table VI. Dosage adjustment guided by serum theophylline concentration. 9 mcg/mL If symptoms are not controlled and current dosage is tolerated, increase dose about 25%. Recheck serum concentration after three days for further dosage adjustment.
¶ If symptoms are not controlled and current dosage is tolerated consider adding additional medication(s) to treatment regimen. 9 mcg/mL Decrease dose by 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment.
25-30 mcg/mL Skip next dose and decrease subsequent doses at least 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment. If symptomatic, consider whether overdose treatment is indicated (see recommendations for chronic over dosage).
>30 mcg/mL Treat overdose as indicated (see recommendations for chronic overdosage). If theophylline is subsequently resumed, decrease dose by at least 50% and recheck serum concentration after 3 days to guide further dosage adjustment.
, sustained fever), or a drug that interacts with theophylline is added or discontinued (see WARNINGS ).
Once-Daily Dosing:
The slow absorption rate of this preparation may allow once-daily administration in adult non-smokers with appropriate total body clearance and other patients with low dosage requirements. Once-daily dosing should be considered only after the patient has been gradually and satisfactorily titrated to therapeutic levels with q12h dosing.
Once-daily dosing should be based on twice the q12h dose and should be initiated at the end of the last q12h dosing interval. The trough concentration (C min ) obtained following conversion to once-daily dosing may be lower (especially in high clearance patients) and the peak concentration (C max ) may be higher (especially in low clearance patients) than that obtained with q12h dosing.
If symptoms recur, or signs of toxicity appear during the once-daily dosing interval, dosing on the q12h basis should be reinstituted. It is essential that serum theophylline concentrations be monitored before and after transfer to once-daily dosing.
Food and posture, along with changes associated with circadian rhythm, may influence the rate of absorption and / or clearance rates of theophylline from extended-release dosage forms administered at night. The exact relationship of these and other factors to nighttime serum concentrations and the clinical significance of such findings require additional study.
Therefore, it is not recommended that theophylline extended-release once-daily dosing be administered at night.
e. they have generally been transient, often stopped without anticonvulsant therapy, and did not result in neurological residua). Table IV. * Percentage of patients reported with sign or symptoms Acute Overdose (Large Single Ingestion) Chronic Overdosage (Multiple Excessive Doses) Sign / Symptom Study 1 (n = 157) Study 2 (n = 14) Study 1 (n = 92) Study 2 (n = 102) Asymptomatic NR** 0 NR** 6 Gastrointestinal Vomiting 73 93 30 61 Abdominal Pain NR** 21 NR** 12 Diarrhea NR** 0 NR** 14 Hematemesis NR** 0 NR** 2 Metabolic/Other Hypokalemia 85 79 44 43 Hyperglycemia 98 NR** 18 NR** Acid/base disturbance 34 21 9 5 Rhabdomyolysis NR** 7 NR** 0 Cardiovascular Sinus tachycardia 100 86 100 62 Other Supraventricular Tachycardias 2 21 12 14 Ventricular premature beats 3 21 10 19 Atrial fibrillation or flutter 1 NR** 12 NR** Multifocal atrial tachycardia 0 NR** 2 NR** Ventricular arrhythmias hemodynamic instability 7 14 40 0 Hypotension/shock NR** 21 NR** 8 Neurologic Nervousness NR** 64 NR** 21 Tremors 38 29 16 14 Disorientation NR** 7 NR** 11 Seizures 5 14 14 5 Death 3 21 10 4 * These data are derived from two studies in patients with serum theophylline concentrations >30 mcg/mL.
In the first study (Study #1 - Shanon, Ann Intern Med 1993; 119:1161-67), data were prospectively collected from 249 consecutive cases of theophylline toxicity referred to a regional poison center for consultation. In the second study (Study #2 - Sessler, Am J Med 1990;88:567-76), data were retrospectively collected from 116 cases with serum theophylline concentrations >30 mcg/mL among 6000 blood samples obtained for measurement of serum theophylline concentrations in three emergency departments.
, in Study #1, 48% of the patients had acute intoxications versus only 10% in Study #2) and different methods of reporting results. ** NR = Not reported in a comparable manner. gov/medwatch.
Dosage Increases:
Increases in the dose of theophylline should not be made in response to an acute exacerbation of symptoms of chronic lung disease since theophylline provides little added benefit to inhaled beta2 -selective agonists and systemically administered cortico-steroids in this circumstance and increases the risk of adverse effects.
A peak steady-state serum theophylline concentration should be measured before increasing the dose in response to persistent chronic symptoms to ascertain whether an increase in dose is safe. Before increasing the theophylline dose on the basis of a low serum concentration, the healthcare professional should consider whether the blood sample was obtained at an appropriate time in relationship to the dose and whether the patient has adhered to the prescribed regimen (see PRECAUTIONS, Laboratory Tests ).
, steady-state serum concentrations may increase disproportionately to the increase in dose), an increase in dose based upon a sub-therapeutic serum concentration measurement should be conservative. In general, limiting dose increases to about 25% of the previous total daily dose will reduce the risk of unintended excessive increases in serum theophylline concentration (see DOSAGE AND ADMINISTRATION, Table VI ).